Emrelis Drug Information
Generic name: TELISOTUZUMAB VEDOTIN
Uses of Emrelis
is indicated for the treatment of adult patients with locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with high c-Met protein overexpression, as determined by an FDA-approved test , who have received a prior systemic therapy. This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR) . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). EMRELIS is a c-Met-directed antibody and microtubule inhibitor conjugate indicated for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) with high c-Met protein overexpression, as determined by an FDA-approved test, who have received a prior systemic therapy. This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Dosage & Administration of Emrelis
| First | 1.6 mg/kg every 2 weeks |
|---|---|
| Second | 1.3 mg/kg every 2 weeks |
| Third | 1 mg/kg every 2 weeks |
| Permanently discontinue EMRELIS in patients who are unable to tolerate 1 mg/kg. | |
Side Effects of Emrelis
Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. LUMINOSITY The safety population described in WARNINGS AND PRECAUTIONS and below reflects exposure to EMRELIS in 168 patients with locally advanced or metastatic EGFR wild-type non-squamous NSCLC with c-Met protein overexpression who received EMRELIS as a single agent administered at 1.9 mg/kg intravenously every 2 weeks in the LUMINOSITY study. Among patients who received EMRELIS, 42% were exposed for 6 months or longer and 11% were exposed for greater than one year.
The median age of patients who received EMRELIS was 64.5 years (range: 33 to 83 years); 70% were male; 65% were White; 1.8% were Black or African American, 33% were Asian; and 0.6% were of Hispanic or Latino ethnicity. Serious adverse reactions occurred in 35% of patients. Serious adverse reactions occurring in ≥2% of patients included ILD/pneumonitis (5%), pneumonia (5%), peripheral neuropathy (3.6%), and pleural effusion (2.4%). Fatal adverse reactions occurred in 5% of patients who received EMRELIS, including ILD/pneumonitis (1.8%), pneumonia (1.2%), sudden death (1.2%), noninfectious endocarditis (0.6%) and myocardial infarction (0.6%). Permanent discontinuations of EMRELIS due to adverse reactions occurred in 30% of patients.
Adverse reactions which resulted in permanent discontinuation of EMRELIS in ≥2% included peripheral neuropathy and ILD/pneumonitis. Dosage interruptions due to adverse reactions occurred in 44% of patients. Adverse reactions which required dosage interruption in ≥2% of patients included peripheral neuropathy, fatigue, pneumonia, increased ALT, blurred vision, COVID-19, ILD/pneumonitis, and keratitis.
Dose reductions due to adverse reactions occurred in 28% of patients. Adverse reactions which required dose reductions in ≥2% of patients included peripheral neuropathy, fatigue, and keratitis. The most common adverse reactions (≥20%) were peripheral neuropathy, fatigue, decreased appetite, and peripheral edema.
The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocytes, increased glucose, increased ALT, increased gamma glutamyl transferase, decreased phosphorus, decreased sodium, decreased hemoglobin and decreased calcium. Table 5 summarizes the adverse reactions in LUMINOSITY. Table 5. Adverse Reactions (≥10%) in Patients with EGFR Wild-Type Non-squamous NSCLC with c-Met Protein Overexpression in LUMINOSITY Adverse Reaction EMRELIS (N=168) All Grades 1 % Grade 3 or 4 1 % Nervous system disorders Peripheral neuropathy 2 51 11 General disorders and administration site conditions Fatigue 2 29
Gastrointestinal disorders Nausea 15 0 Constipation 14 0.6 Vomiting 10 0.6 Eye
disorders Blurred vision 3 15
Keratitis 4 11 0.6 Infections and infestations Pneumonia 2 13 6 Respiratory
thoracic and mediastinal disorders ILD/pneumonitis 2 10 3.6 1 Events were graded using NCI CTCAE version 4.03. 2 Grouped term. 3 Includes vision blurred, visual acuity reduced, visual impairment. 4 Includes corneal cyst, corneal disorder, corneal erosion, corneal edema, corneal opacity, keratitis, keratitis interstitial, punctate keratitis. Other clinically relevant adverse reactions in <10% of patients who received EMRELIS included arthralgia, dizziness, dry eye, infusion-related reaction and photophobia. Table 6 presents laboratory abnormalities in LUMINOSITY. Table 6. Select Laboratory Abnormalities (≥10%) that Worsened from Baseline in Patients with EGFR Wild-Type Non-squamous NSCLC with c-Met Protein Overexpression in LUMINOSITY Laboratory Abnormality EMRELIS (N=168) All Grades % Grade 3 or 4 % Chemistry Albumin decreased 61
Gamma glutamyl transferase increased 36 4.3 Aspartate aminotransferase increased 34 0.6 Phosphorus
decreased 33
Potassium decreased 14 1.2 Magnesium decreased 14 0.6 Glucose decreased 11 0
Magnesium increased 10 0 Hematology Lymphocytes decreased 37 10 Hemoglobin decreased 35
White blood cells decreased 16 1.2 Platelets decreased 14 0.6 Neutrophils decreased
10
Percentages were calculated using patients with worsening laboratory values from baseline and
the number of patients with both baseline and post-treatment measurements as the denominator.
Warnings & Cautions for Emrelis
Peripheral Neuropathy
EMRELIS can cause peripheral neuropathy, including peripheral sensory neuropathy and peripheral motor neuropathy. In the safety population, peripheral neuropathy occurred in 51% of patients treated with EMRELIS, including Grade 3 in 11%. These adverse reactions included peripheral sensory neuropathy in 45% of patients and peripheral motor neuropathy in 9%. The median time to onset of peripheral neuropathy was 105 days (range: 1 to 472 days). Peripheral neuropathy led to permanent discontinuation of EMRELIS in 13% of patients. The median time to onset of peripheral neuropathy leading to treatment discontinuation was 249 days (range: 57 to 519 days). Of the 7 patients with motor neuropathy ongoing as of their last dose of EMRELIS, 6 had persistent Grade 1 or 2 symptoms 30 days after their last dose.
Monitor patients for signs and symptoms of new or worsening peripheral neuropathy such as hypoesthesia, hyperesthesia, paresthesia, a burning sensation, neuropathic pain, or muscle weakness. Withhold, reduce the dose or permanently discontinue EMRELIS based on severity.
Interstitial Lung Disease /Pneumonitis
EMRELIS can cause severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis. In the safety population, ILD/pneumonitis occurred in 10% of patients treated with EMRELIS, including Grade 3 in 3% and Grade 4 in 0.6%. There were 3 fatal cases of ILD/pneumonitis in patients who received EMRELIS. The median time to onset of ILD/pneumonitis was 48 days (range: 23 to 85 days). ILD/pneumonitis led to permanent discontinuation of EMRELIS in 7% of patients. The median time to onset of ILD/pneumonitis leading to treatment discontinuation was 46 days (range: 23 to 85 days). Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms.
Monitor patients for signs and symptoms of ILD/pneumonitis. Withhold or permanently discontinue EMRELIS based on severity.
Ocular Surface Disorders
EMRELIS can cause ocular surface disorders including blurred vision, visual impairment, keratitis, and dry eye. In the safety population, ocular surface disorders occurred in 25% of patients treated with EMRELIS. The most common ocular surface disorders were blurred vision (15%), keratitis (11%), and dry eye (5%). Grade 3 ocular surface disorders occurred in 1.2% of patients. The median time to onset of ocular surface disorders was 47 days (range: 1 to 319 days). Monitor patients for ocular surface disorders during treatment with EMRELIS. Withhold EMRELIS and refer patients to an eye care professional for an ophthalmic examination and treatment for patients who develop Grade ≥2 ocular toxicity.
Withhold or permanently discontinue EMRELIS based on severity.
Infusion - Related Reactions
EMRELIS can cause infusion-related reactions (IRR); signs and symptoms of IRR include dyspnea, flushing, chills, nausea, chest discomfort, and hypotension. The median time to onset of IRR was 28 days (range: 1 to 43 days). In the safety population, , IRR occurred in 3% of patients treated with EMRELIS including Grade 3 in 1.2% and Grade 4 in 0.6%. IRR led to permanent discontinuation of EMRELIS in 0.6% of patients. Monitor patients for signs and symptoms of infusion reactions during EMRELIS infusion.
Withhold, reduce the rate of infusion, or permanently discontinue EMRELIS based on severity. For patients who experience IRR, administer premedications prior to subsequent infusions. 5. 5 Embryo-Fetal Toxicity Based on the mechanism of action and findings in animals, EMRELIS can cause fetal harm when administered to a pregnant woman. The small molecule component of EMRELIS, MMAE, administered to rats caused adverse developmental outcomes, including embryo-fetal mortality and structural abnormalities, at exposures similar to those occurring clinically at the recommended dose.
Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with EMRELIS and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with EMRELIS and for 4 months after the last dose.
Drug Interactions with Emrelis
Effect of Other Drugs on
EMRELIS Strong CYP3A Inhibitors Concomitant use with strong CYP3A inhibitors may increase unconjugated MMAE AUC , which may increase the risk of EMRELIS adverse reactions. Monitor patients for adverse reactions when EMRELIS is given concomitantly with strong CYP3A inhibitors.
Pregnancy Safety for Emrelis
Pregnancy Risk Summary Based on the mechanism of action and findings in animals, EMRELIS can cause fetal harm when administered to a pregnant woman . There are no available human data on EMRELIS use in pregnant women to inform a drug-associated risk. In an animal reproduction study, administration of the small molecule component of EMRELIS, MMAE, to pregnant rats during organogenesis resulted in embryo-fetal mortality and structural abnormalities at exposures similar to the clinical exposure at the recommended dose . Advise patients of the potential risks to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data Animal Data No embryo-fetal development studies in animals have been performed with telisotuzumab vedotin-tllv. In an embryo-fetal development study in pregnant rats, administration of two intravenous doses of MMAE, the small molecule component of EMRELIS, on gestational days 6 and 13 caused embryo-fetal mortality and structural abnormalities, including protruding tongue, agnathia, malrotated limbs, and gastroschisis compared to controls at a dose of 0.2 mg/kg (approximately 2 times the human area under the curve at the recommended dose).
Pediatric Use of Emrelis
Pediatric Use Safety and effectiveness of EMRELIS have not been established in pediatric patients.
Clinical Studies of Emrelis
DOR ≥6 months, a % 59
DOR ≥12 months, a % 21 CI=confidence interval; DOR=duration of response a Based on observed duration of response in 29 responders.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
Ready to save on Emrelis?
Compare prescription prices at over 70,000 pharmacies and start saving today—no enrollment required.
Compare Emrelis Prices